POS0553 NEW BIOMARKERS IN RHEUMATOID ARTHRITIS: ROLE OF HOMOCYSTEINYLATED ANTI-ALPHA1 ANTITRYPSIN ANTIBODIES
Authors: M. Speziali, F. Ceccarelli, F. Natalucci, A. I. Celia, T. Colasanti, C. Barbati, G. Olivieri, E. Balbinot, C. Ciancarella, F. M. Ucci, G. Buoncuore, G. Tripdi, F. R. Spinelli, F. Conti, C. Alessandri
Journal: Annals of the Rheumatic Diseases (2022)

Background Rheumatoid Arthritis (RA) is a multifactorial, chronic, systemic, inflammatory disease that can lead to progressive joint destruction (Alamanos et al, Autoimmun Rev 2005). Positivity for Rheumatoid Factor (RF) and antibodies against citrullinated proteins (ACPA) is useful for diagnostic and prognostic purposes. Nevertheless, in about 20% of patients, it is not possible to detect the presence of these autoantibodies. This has led to the identification of new antibody specificities, such as antibodies directed against carbamylated proteins (Mastrangelo A et al, J Immunol Res 2015) and, more recently, against homocysteinylated alpha 1 antitrypsin (anti-HATA) (Colasanti T et al, J Autoimmun 2020). Objectives To evaluate the prevalence of anti-HATA in a large cohort of patients with RA and their correlation with serological, clinical and erosive bone damage assessed by musculo-skeletal ultrasound (US). Methods Consecutive outpatients with RA, diagnosed according to the 2010 ACR/EULAR criteria, were enrolled. Demographic and clinical-laboratory data were recorded, including FR and ACPA determination. Disease activity was assessed by DAS28. The presence of anti-HATA antibodies was investigated by homemade ELISA using native alpha 1 antitrypsin modified in vitro to obtain homocysteinylated alpha 1 antitrypsin. US assessment was performed at the level of bilateral metacarpophalangeal and proximal interphalangeal joints; the presence of erosions and inflammatory features was identified according to OMERACT definitions (Wakefield RJ et al, J Rheumatol 2005). Results The present analysis included 91 RA patients (M/F 22/69; mean age 62 years; mean disease duration 12.5 years). Overall, the prevalence of anti-HATA was 69.2%. Anti-HATA antibodies were found in 63/91 (69.2%) of the entire patient cohort, whereas 68/91 (74.3%) patients were positive for ACPA and 63/91 (69.4%) for FR. 41.4% of patients had concomitant positivity for the three autoantibodies (FR, ACPA, anti-HATA). The analysis of patients with triple positivity for related arthritis antibodies (FR, ACPA, anti-HATA) was particularly interesting: indeed, in this subgroup, 80% of patients presented erosive damage, compared to 42.1% of patients who did not present simultaneously the three autoantibodies (p=0.0001). Patients with simultaneous positivity for RF, ACPA and anti-HATA showed a more aggressive disease phenotype (p=0.0001). Finally, a positive correlation was also found between disease activity (expressed by DAS28) and total inflammatory and erosive ultrasonographic score (p=0.005 and p=0.001, respectively). Conclusion The results of the present study confirm a high prevalence of anti-HATA in RA patients; furthermore, patients with concomitant presence of anti-HATA, ACPA and RF showed a more aggressive disease phenotype, in terms of erosive damage. Our analysis underlines as the characterization of new antibody specificities in RA could help in the early diagnosis of this disease and in the characterization of the different severity degrees. References [1]Alamanos Y, Drosos AA. Epidemiology of adult rheumatoid arthritis. Autoimmun Rev. 2005 Mar;4(3):130-6. [2]Mastrangelo A, Colasanti T, Barbati C, Pecani A, Sabatinelli D, Pendolino M, Truglia S, Massaro L, Mancini R, Miranda F, Spinelli FR, Conti F, Alessandri C. The Role of Posttranslational Protein Modifications in Rheumatological Diseases: Focus on Rheumatoid Arthritis. J Immunol Res. 2015;2015:712490; [3]Colasanti T, Sabatinelli D, Mancone C, Giorgi A, Pecani A, Spinelli FR, Di Giamberardino A, Navarini L, Speziali M, Vomero M, Barbati C, Perricone C, Ceccarelli F, Finucci A, Celia AI, Currado D, Afeltra A, Schininà ME, Barnaba V, Conti F, Valesini G, Alessandri C. Homocysteinylated alpha 1 antitrypsin as an antigenic target of autoantibodies in seronegative rheumatoid arthritis patients. J Autoimmun. 2020 Sep;113:102470. [4]Wakefield RJ, Balint PV, Szkudlarek M, et al. Musculoskeletal ultrasound including definitions for ultrasonographic pathology. J Rheumatol 2005; 32: 2485-2487. Disclosure of Interests None declared.